Bioassay of 2,4,6-Trichlorophenol for Possible Carcinogenicity (CAS No. 88-06-2)
Chemical Formula: C6H3Cl3O
2,4,6-Trichlorophenol is a germicidal agent that has been used to preserve wood and glue as well as to protect textiles against mildew. Production of this chemical (for sale as an end product) was discontinued in 1975 by Dow Chemical Company, the only manufacturer of 2,4,6-trichlorophenol in the United States, because of the high cost of removing toxic dioxin impurities. However, a small quantity (2,204 pounds) was imported for domestic use in 1976.
A bioassay of 2,4,6-trichlorophenol for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice.
Groups of 50 rats of each sex were administered 2,4,6-trichlorophenol at one of two doses, either 5,000 or 10,000 ppm, for 106 or 107 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of administration of the test chemical.
Groups of 50 male mice were administered 2,4,6-trichlorophenol at one of two doses, either 5,000 or 10,000 for 105 weeks. Groups of 50 female mice were administered the test chemical at one of two doses, initially either 10,000 or 20,000 ppm, for 38 weeks. Because of excessively lowered body weights in the dosed groups of the females, the doses for the females were then reduced to 2,500 and 5,000 ppm, respectively, and administration at the lower doses was continued for 67 weeks. The time-weighted average doses for the female mice were either 5,214 or 10,428 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of administration of the test chemical.
Mean body weights of dosed rats and mice of each sex were lower than those of corresponding controls and were dose related throughout the bioassay. Survivals to the end of the experiment were 68% or greater in all groups of rats and 80% or greater in all groups of mice.
In the male rats, lymphomas or leukemias occurred at incidences that were dose related (P=0.006) and in direct comparisons were significantly higher in the low-dose(P=0.019) and high-dose (P=0.004) groups than in the corresponding control group (controls 4/20; low-dose 25/50; high-dose 29/50). Leukocytosis and monocytosis of the peripheral blood and hyperplasia of the bone marrow also occurred in some dosed male rats not having lymphoma or leukemia.
In female rats, monocytic leukemia did not occur at incidences that were significant. However, as in the male rats, leukocytosis and monocytosis of the peripheral blood and hyperplasia of the bone marrow occurred in the dosed female rats but not in the controls (blood leukocytosis and monocytosis: controls 0/20, low-dose 6/50, high-dose 3/50; bone marrow hyperplasia: controls 0/20, low-dose 16/50, high-dose 2/50).
In both the male and female mice, hepatocellular carcinomas or adenomas occurred at incidences that were dose related (P<0.001), and in direct comparisons were significantly higher in the low- and high-dose male groups and the high-dose female group (P< 0.001) than in the corresponding control groups (males: controls 4/20, low-dose 32/49, high-dose 39/47; females: controls 1/20, low-dose 12/50, high-dose 24/48).
It is concluded that under the conditions of this bioassay, 2,4,6-trichlorophenol was carcinogenic in male F344 rats, inducing lymphomas or leukemias. The test chemical was also carcinogenic in both sexes of B6C3F1 mice, inducing hepatocellular carcinomas or adenomas.
Report Date: 1979